tbuckley/cabot-search huggingface dataset:
Improving Rectal Cancer Treatments 1 Study at a Time
Authors: Noam VanderWalde, Axel Grothey
Journal: JAMA Network Open (2023)

Markus Diefenhardt, MD; Daniel Martin, MD; Maximilian Fleischmann, MD; Ralf-Dieter Hofheinz, MD; Michael Ghadimi, MD; Claus Rödel, MD; Emmanouil Fokas, MD, DPhil
How to recognize and manage skin toxicities associated with immune checkpoint inhibitors: a practical approach
Authors: Anusuya Kawsar, Khawar Hussain, Andrew James Muinonen-Martin, Louise Fearfield
Journal: British Journal of Dermatology (2023)

Abstract Immune checkpoint inhibitors (ICIs) have revolutionized treatment strategies in the field of oncology. Their favourable outcomes in terms of efficacy and side-effect profile can be thwarted by the development of immune-related adverse events (irAEs). Cutaneous irAEs are relatively common in patients undergoing immunotherapy and include common inflammatory dermatoses (e.g. eczematous, psoriasiform and lichenoid phenotypes), maculopapular eruptions, pruritus and immunobullous disorders. Most of these reactions can be managed without ICIs having to be stopped completely; however, there are some life-threatening toxicities that dermatologists and oncologists should be aware of. In this review, we focus on how to recognize the commonly associated cutaneous irAEs, touching upon rarer reactions and red flags; finally, we provide guidance on their management.
Association of Parental Status and Gender With Burden of Multidisciplinary Tumor Boards Among Oncology Physicians
Authors: Brittney L. Chau, Jonnby S. LaGuardia, Sungjin Kim, Samuel C. Zhang, Eric Pletcher, Nina N. Sanford, Ann C. Raldow, Lisa Singer, Jun Gong, Sukhmani K. Padda, Mitchell Kamrava, Tara Cohen, Devarati Mitra, Katelyn M. Atkins
Journal: JAMA Network Open (2023)

Tumor boards are integral to the care of patients with cancer. However, data investigating the burden of tumor boards on physicians are limited.
Fine-Tuning Adjuvant Endocrine Therapy for Early-Stage Breast Cancer: An Expert Consensus on Open Issues for Future Research
Authors: Fabio Conforti, Laura Pala, Tommaso De Pas, Emma Zattarin, Chiara Catania, Emilia Cocorocchio, Giovanna Rossi, Daniele Laszlo, Marco Colleoni, Alberto Zambelli, Gabriel N. Hortobagyi, Javier Cortes, Martine J. Piccart, Mitch Dowsett, Richard D. Gelber, Giuseppe Viale
Journal: Clinical Cancer Research (2023)

Abstract After decades of research, improving the efficacy of adjuvant endocrine therapy (ET) for early-stage breast cancer becomes increasingly difficult. Beyond technological breakthroughs and the availability of new classes of drugs, further improvement of adjuvant ET will require applying a rigorous research approach in poorly investigated areas. We critically discuss some key principles that should inform future research to improve ET efficacy, including identifying specific subgroups of patients who can benefit from escalating or de-escalating approaches, optimizing available and new treatment strategies for different clinical contexts, and dissecting the direct and indirect biological effects of therapeutic interventions. Four main issues regarding adjuvant ET were identified as relevant areas, where a better application of such principles can provide positive results in the near future: (i) tailoring the optimal duration of adjuvant ET, (ii) optimizing ovarian function suppression for premenopausal women, (iii) dissecting the biological effects of estrogen receptor manipulation, and (iv) refining the selection of patients to candidate for treatments escalation.
Tenofovir vs Entecavir Among Patients With HBV-Related HCC After Resection
Authors: Pengpeng Li, Yuanyuan Wang, Jian Yu, Judian Yu, Qifei Tao, Jinwei Zhang, Wan Yee Lau, Weiping Zhou, Gang Huang
Journal: JAMA Network Open (2023)

Tenofovir disoproxil and entecavir are both commonly used first-line antiviral treatments, but their comparative recurrence and overall survival (OS) benefits remain unclear.To explore differences of tenofovir disoproxil vs entecavir in recurrence-free survival (RFS) and OS after liver resection with curative intent in patients with hepatocellular cancer (HCC) related to hepatitis B virus (HBV).This retrospective cohort study was conducted at Eastern Hepatobiliary Surgery Hospital, a tertiary referral hospital in Shanghai, China, between January 4, 2015, and April 1, 2023. Participants included patients with HBV-related HCC who underwent liver resection with curative intent from January 2015 to December 2018. Patients who received tenofovir disoproxil were matched with patients who received entecavir in a 1:1 ratio using propensity score matching. Data were analyzed from April 3 to May 31, 2023.Receiving tenofovir disoproxil or entecavir as antiviral treatment for HBV.Primary end points were RFS and OS rates.Among 4451 patients (mean [SD] age, 58.1 [10.0] years; 3764 male [84.6%]; median [range] follow-up, of 51 [3 to 91] months), 989 patients in each of the groups were selected in propensity score matching. Baseline characteristics were comparable. In propensity score-matched groups, OS rates were 92.2% at 1 year, 70.9% at 3 years, and 54.2% at 5 years in the entecavir group, compared with 90.9% at 1 year, 75.2% at 3 years, and 64.0% at 5 years in the tenofovir disoproxil group. RFS rates were 83.9% at 1 year, 50.0% at 3 years, and 43.3% at 5 years in the entecavir group, compared with 85.3% at 1 year, 55.6% at 3 years, and 51.4% at 5 years in the tenofovir disoproxil group. Patients in the tenofovir disoproxil group had better OS (hazard ratio, 0.82; 95% CI, 0.72 to 0.94; P = .004) and RFS rates (hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = .001) compared with the entecavir group. Restricted mean survival time differences of entecavir vs tenofovir disoproxil groups were -0.05 (95% CI, -0.18 to 0.08) months at 1 year (P = .45), 0.20 (95% CI, -0.62 to 1.03) months at 3 years (P = .63), and 1.82 (95% CI, 0.14 to 3.51) months at 5 years (P = .03).These findings suggest that in patients undergoing curative liver resection for HBV-related HCC, tenofovir disoproxil was associated with better long-term OS and RFS rates compared with entecavir, providing insights for antiviral treatment.
Use, Potential Use, and Awareness of the 988 Suicide and Crisis Lifeline by Level of Psychological Distress
Authors: Jonathan Purtle, Anna-Michelle Marie McSorley, Abigail Lin Adera, Michael A. Lindsey
Journal: JAMA Network Open (2023)

This cross-sectional study assesses variations in use, potential use, and awareness of the 988 Suicide and Crisis Lifeline among people with varying levels of psychological distress.
ChaMP-CMD: A Phenotype-Blinded, Randomized Controlled, Cross-Over Trial
Authors: Aish Sinha, Haseeb Rahman, Abdel Douiri, Ozan M. Demir, Kalpa De Silva, Brian Clapp, Ian Webb, Ankur Gulati, Pedro Pinho, Utkarsh Dutta, Howard Ellis, Ajay M. Shah, Amedeo Chiribiri, Michael Marber, Andrew J. Webb, Divaka Perera
Journal: Circulation (2023)

Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy.
Use of Urea for the Syndrome of Inappropriate Secretion of Antidiuretic Hormone
Authors: Ralph Wendt, Andrew Z. Fenves, Benjamin P. Geisler
Journal: JAMA Network Open (2023)

Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and safety of oral urea for SIADH are still debated.
<i>The</i><i> Autumn Ghost</i>—The Danish Polio Epidemic of 1952 and the Birth of Intensive Care Medicine
Authors: David Oshinsky
Journal: JAMA (2023)

This Arts and Medicine feature reviews The Autumn Ghost, an historical retelling of the 1952 polio epidemic in Copenhagen, Denmark, which catalyzed developments in anesthesia and respiratory support procedures that are still in use today.
First-in-human therapy with Treg produced from thymic tissue (thyTreg) in a heart transplant infant
Authors: Esther Bernaldo-de-Quirós, Manuela Camino, Marta Martínez-Bonet, Juan Miguel Gil-Jaurena, Nuria Gil, Diana Hernández-Flórez, Maria Eugenia Fernández-Santos, Laura Butragueño, I. Esmé Dijke, Megan K. Levings, Lori J. West, Marjorie Pion, Rafael Correa-Rocha
Journal: The Journal of Experimental Medicine (2023)

Due to their suppressive capacity, regulatory T cells (Tregs) have attracted growing interest as an adoptive cellular therapy for the prevention of allograft rejection, but limited Treg recovery and lower quality of adult-derived Tregs could represent an obstacle to success. To address this challenge, we developed a new approach that provides large quantities of Tregs with high purity and excellent features, sourced from thymic tissue routinely removed during pediatric cardiac surgeries (thyTregs). We report on a 2-year follow-up of the first patient treated worldwide with thyTregs, included in a phase I/II clinical trial evaluating the administration of autologous thyTreg in infants undergoing heart transplantation. In addition to observing no adverse effects that could be attributed to thyTreg administration, we report that the Treg frequency in the periphery was preserved during the 2-year follow-up period. These initial results are consistent with the trial objective, which is to confirm safety of the autologous thyTreg administration and its capacity to restore the Treg pool.
Emotion recognition in relation to tumor characteristics in patients with low-grade glioma
Authors: Femke F Siebenga, Hiska L van der Weide, Floor Gelmers, Sandra E Rakers, Miranda C A Kramer, Anouk van der Hoorn, Roelien H Enting, Ingeborg Bosma, Rob J M Groen, Hanne-Rinck Jeltema, Michiel Wagemakers, Jacoba M Spikman, Anne M Buunk
Journal: Neuro-Oncology (2023)

Abstract Background Patients with low-grade gliomas (LGG) treated with surgery, generally function well and have a favorable prognosis. However, LGG can affect neurocognitive functioning. To date, little is known about social cognition (SC) in these patients, although impaired SC is related to social-behavioral problems and poor societal participation. Frontal brain areas are important for SC and LGG frequently have a frontal location. Therefore, the aim of the present study was to investigate whether emotion recognition, a key component of SC, was impaired, and related to general cognition, tumor location, laterality, tumor volume, and histopathological characteristics in patients with LGG, postsurgery, and before start of adjuvant therapy. Methods A total of 121 patients with LGG were matched with 169 healthy controls (HC). Tumor location [including (frontal) subregions; insula, anterior cingulate cortex, lateral prefrontal cortex (LPFC), orbitofrontal-ventromedial PFC] and tumor volume were determined on MRI scans. Emotion recognition was measured with the Ekman 60 faces test of the Facial Expressions of Emotion-Stimuli and Tests (FEEST). Results Patients with LGG performed significantly lower on the FEEST than HC, with 33.1% showing impairment compared to norm data. Emotion recognition was not significantly correlated to frontal tumor location, laterality, and histopathological characteristics, and significantly but weakly with general cognition and tumor volume. Conclusions Emotion recognition is impaired in patients with LGG but not (strongly) related to specific tumor characteristics or general cognition. Hence, measuring SC with individual neuropsychological assessment of these patients is crucial, irrespective of tumor characteristics, to inform clinicians about possible impairments, and consequently offer appropriate care.
Trends in Cardiovascular Disease Mortality in US Women Veterans vs Civilians
Authors: Ramin Ebrahimi, Elizabeth M. Yano, Carlos A. Alvarez, Paul A. Dennis, A. Laurie Shroyer, Jean C. Beckham, Jennifer A. Sumner
Journal: JAMA Network Open (2023)

Importance Cardiovascular disease (CVD) remains the leading cause of death in the US. Women veterans have higher rates of CVD compared with civilian US women; however, analyses of recent trends in mortality from cardiac disease for women veterans are lacking. Objective To investigate trends in cardiac disease mortality among women veterans over approximately the past 2 decades and compare rates with those for civilian women. Design, Setting, and Participants In this retrospective longitudinal cohort study, US Veterans Health Administration (VHA) electronic health record data, linked with the National Death Index, were analyzed for CVD trends and rates of cardiac disease mortality among women veterans (aged 18 years or older) with VHA health care encounters from January 1, 2000, to December 31, 2017. These data were compared with a national cohort of civilian women (aged 15 years or older) in the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database, which provides cause-of-death data using death certificates for all US residents. The data analysis was performed between March 10, 2021, and November 28, 2022. Exposure Cardiac disease mortality among women veterans and civilian women. Main Outcomes and Measures Cardiac disease mortality was based on International Classification of Diseases, Tenth Revision diagnostic codes (I00-I09, I11, I13, and I20-I51 as defined by CDC WONDER). For women veterans and civilian women, crude and age-adjusted cardiac disease mortality rates (per 100 000 life-years) and 95% CIs were calculated, with the 2000 US general population as the reference for age-adjusted rates. Results From 2000 to 2017, 817 912 women veterans engaged with VHA health care (mean [SD] age, 45.7 [17.1] years), and 19 022 cardiac disease deaths were identified (22.4% of total deaths). The crude and age-adjusted cardiac disease mortality rates, respectively, per 100 000 life-years were 200.2 (95% CI, 181.0-221.0) and 197.6 (95% CI, 175.2-222.0) in 2000 and 196.0 (95% CI, 186.1-206.4) and 208.1 (95% CI, 196.4-220.4) in 2017, reflecting stable crude rates and a 5.3% increase in age-adjusted rates. For civilian women, the crude and age-adjusted rates decreased over time from 320.7 (95% CI, 319.7-321.8) and 268.1 (95% CI, 267.3-269.0) in 2000 to 220.9 (95% CI, 220.1-221.7) and 164.7 (95% CI, 164.1-165.3) in 2017. Conclusions and Relevance In this cohort study comparing women veterans and civilian women, cardiac disease mortality rates for women veterans did not exhibit the improvements seen for civilian women during the nearly 2-decade study period. Further research and actionable clinical interventions are warranted to improve cardiovascular care for women veterans, who represent the fastest growing group of patients within the VHA health care system.
PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy
Authors: Xuefeng Dou, Qiang Fu, Qilai Long, Shuning Liu, Yejun Zou, Da Fu, Qixia Xu, Zhirui Jiang, Xiaohui Ren, Guilong Zhang, Xiaoling Wei, Qingfeng Li, Judith Campisi, Yuzheng Zhao, Yu Sun
Journal: Nature Metabolism (2023)

Abstract Senescent cells remain metabolically active, but their metabolic landscape and resulting implications remain underexplored. Here, we report upregulation of pyruvate dehydrogenase kinase 4 (PDK4) upon senescence, particularly in some stromal cell lines. Senescent cells display a PDK4-dependent increase in aerobic glycolysis and enhanced lactate production but maintain mitochondrial respiration and redox activity, thus adopting a special form of metabolic reprogramming. Medium from PDK4 + stromal cells promotes the malignancy of recipient cancer cells in vitro, whereas inhibition of PDK4 causes tumor regression in vivo. We find that lactate promotes reactive oxygen species production via NOX1 to drive the senescence-associated secretory phenotype, whereas PDK4 suppression reduces DNA damage severity and restrains the senescence-associated secretory phenotype. In preclinical trials, PDK4 inhibition alleviates physical dysfunction and prevents age-associated frailty. Together, our study confirms the hypercatabolic nature of senescent cells and reveals a metabolic link between cellular senescence, lactate production, and possibly, age-related pathologies, including but not limited to cancer.
Incidence, risk assessment and prevention of sudden cardiac death in cardiomyopathies
Authors: Marija Polovina, Carsten Tschöpe, Giuseppe Rosano, Marco Metra, Filippo Crea, Wilfried Mullens, Johann Bauersachs, Karen Sliwa, Rudolf A. de Boer, Dimitrios Farmakis, Thomas Thum, Domenico Corrado, Antoni Bayes‐Genis, Biykem Bozkurt, Gerasimos Filippatos, Andre Keren, Hadi Skouri, Brenda Moura, Maurizio Volterrani, Magdy Abdelhamid, Milika Ašanin, Gordana Krljanac, Milenko Tomić, Gianluigi Savarese, Marianna Adamo, Yuri Lopatin, Ovidiu Chioncel, Andrew J.S. Coats, Petar M. Seferović
Journal: European Journal of Heart Failure (2023)
DeepGAMI: deep biologically guided auxiliary learning for multimodal integration and imputation to improve genotype–phenotype prediction
Authors: Pramod Bharadwaj Chandrashekar, Sayali Alatkar, Jiebiao Wang, Gabriel E. Hoffman, Chenfeng He, Ting Jin, Saniya Khullar, Jaroslav Bendl, John F. Fullard, Panos Roussos, Daifeng Wang
Journal: Genome Medicine (2023)

Abstract Background Genotypes are strongly associated with disease phenotypes, particularly in brain disorders. However, the molecular and cellular mechanisms behind this association remain elusive. With emerging multimodal data for these mechanisms, machine learning methods can be applied for phenotype prediction at different scales, but due to the black-box nature of machine learning, integrating these modalities and interpreting biological mechanisms can be challenging. Additionally, the partial availability of these multimodal data presents a challenge in developing these predictive models. Method To address these challenges, we developed DeepGAMI, an interpretable neural network model to improve genotype–phenotype prediction from multimodal data. DeepGAMI leverages functional genomic information, such as eQTLs and gene regulation, to guide neural network connections. Additionally, it includes an auxiliary learning layer for cross-modal imputation allowing the imputation of latent features of missing modalities and thus predicting phenotypes from a single modality. Finally, DeepGAMI uses integrated gradient to prioritize multimodal features for various phenotypes. Results We applied DeepGAMI to several multimodal datasets including genotype and bulk and cell-type gene expression data in brain diseases, and gene expression and electrophysiology data of mouse neuronal cells. Using cross-validation and independent validation, DeepGAMI outperformed existing methods for classifying disease types, and cellular and clinical phenotypes, even using single modalities (e.g., AUC score of 0.79 for Schizophrenia and 0.73 for cognitive impairment in Alzheimer’s disease). Conclusion We demonstrated that DeepGAMI improves phenotype prediction and prioritizes phenotypic features and networks in multiple multimodal datasets in complex brains and brain diseases. Also, it prioritized disease-associated variants, genes, and regulatory networks linked to different phenotypes, providing novel insights into the interpretation of gene regulatory mechanisms. DeepGAMI is open-source and available for general use.
Impact of<i>Helicobacter pylori</i>infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors
Authors: Patrick T Magahis, Steven B Maron, Darren Cowzer, Stephanie King, Mark Schattner, Yelena Janjigian, David Faleck, Monika Laszkowska
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Gut microbiota composition can influence cancer immunotherapy response. Recent evidence suggests Helicobacter pylori infection may reduce immune checkpoint inhibitor (ICI) efficacy in lung cancer and melanoma, but thorough characterization of this association in patients with gastric cancer is lacking. We aimed to determine the impact of H. pylori on survival in this population. Methods This single-center, retrospective study included all ICI-treated individuals with metastatic gastric cancer and documented H. pylori status at Memorial Sloan Kettering between July 2013 and October 2021. H. pylori -positive status was defined as history of infection obtained via breath test, stool antigen test, histopathology, and/or chart documentation. Negative status was defined as explicitly negative testing, histopathology, and/or chart documentation. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Results Of 215 included patients, 49 had documented history of H. pylori infection. Compared with H. pylori- negative patients, positive individuals tended to be younger, non-white, and Hispanic with non-cardia and intestinal-type gastric cancer. H. pylori- positive patients had significantly shorter median PFS (3.2 vs 6.8 months, HR 1.96, p&lt;0.01) and OS (9.8 vs 17.9 months, HR 1.54, p=0.02). Multivariable analysis confirmed H. pylori infection as an independent predictor of PFS (HR 3.04, p&lt;0.01) and OS (HR 2.24, p=0.01). Conclusions In this largest study of its kind, H. pylori infection was associated with inferior survival in ICI-treated patients with gastric cancer. This suggests H. pylori status may be a prognostic marker of immune responsiveness. Future studies are needed to elucidate immunoregulatory mechanisms and whether treatment of active infections would improve immunotherapy outcomes.
Effectiveness of Nirmatrelvir–Ritonavir Against the Development of Post–COVID-19 Conditions Among U.S. Veterans
Authors: George N. Ioannou, Kristin Berry, Nallakkandi Rajeevan, Yuli Li, Pradeep Mutalik, Lei Yan, David Bui, Francesca Cunningham, Denise M. Hynes, Mazhgan Rowneki, Amy Bohnert, Edward J. Boyko, Theodore J. Iwashyna, Matthew L. Maciejewski, Thomas F. Osborne, Elizabeth M. Viglianti, Mihaela Aslan, Grant D. Huang, Kristina L. Bajema
Journal: Annals of Internal Medicine (2023)

COVID-19 has been linked to the development of many post-COVID-19 conditions (PCCs) after acute infection. Limited information is available on the effectiveness of oral antivirals used to treat acute COVID-19 in preventing the development of PCCs.